Short term treatment with estradiol decreases the rate of newly generated cells in the subventricular zone and main olfactory bulb of adult female mice

Abstract

Abstract-Adult neurogenesis occurs most notably in the subgranular zone (SGZ) of the hippocampal dentate gyrus and in the olfactory bulb (OB) where new neurons are generated from neural progenitors cells produced in the subventricular zone (SVZ) of the forebrain. As it is well known that gonadal steroid hormones, primarily estradiol, modulate neurogenesis in the hippocampus of adult female rodents, we wanted to determine whether estradiol would also affect the proliferation of progenitor cells in the SVZ and by consequence the rate of newly generated cells in the main OB. Thus a first group of adult female C57Bl6/J mice was ovariectomized and received a short term treatment with estradiol (single injection of 1 or 10 g 17␤-estradiol or Silastic capsule of estradiol during 2 days) before receiving a single injection with BrdU to determine whether estradiol would modulate the cell proliferation in the SVZ. A second group of adult ovariectomized female mice was submitted to the same estradiol treatment before receiving four BrdU injections, and was sacrificed 21 days later to determine whether a modulation in cell proliferation actually leads to a modulation in the number of newborn cells in the main OB. We observed a decrease in cell proliferation in the SVZ following either dose of estradiol compared to the controls. Furthermore, 21 days after their generation in the SVZ, the number of BrdU labeled cells was also lower in the main OB, both in the granular and periglomerular cell layers of estradiol-treated animals. These results show that a short term treatment with estradiol actually downregulates cell proliferation leading to a decreased number of newborn cells in the OB.

Testosterone and estradiol differentially affect cell proliferation in the subventricular zone of young adult gonadectomized male and female rats

“…By contrast, in C57Bl/6j/sv129 female mice chronically exposed to E 2 , newborn cell survival in the OB decreases and SVZ cell proliferation is not modified (Veyrac and Bakker, 2011). On the contrary, a short-term exposure to E 2 negatively affects cell proliferation in C57Bl6/J female mice SVZ (Brock et al, 2010). Interestingly, in OVX female mice of the same strain, a chronic treatment with low doses of E 2 stimulates cell proliferation in the SVZ of post-stroke animals, although such increase was not present in control animals (Suzuki et al, 2007).…”

“…Here we focused on the SVZ neurogenic niche, which generate newborn neurons fated to the OB region (Tong andAlvarez-Buylla, 2014, Hamson et al, 2013). Surprisingly, only a 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 14 few studies are at the moment available concerning the impact of gonadal hormones on OB neurogenesis (Smith et al, 2001, Hoyk et al, 2006, Brock et al, 2010, Veyrac and Bakker, 2011, despite their contribution to olfactory reproductive behavior (Keller et al, 2009), and recent data supporting a link between OB neurogenesis and reproduction (reviewed in Peretto and Paredes, 2014).…”

“…Gonadal hormones have been indicated as important intrinsic regulative factors of adult neurogenesis (Galea, 2008. The vast majority of the studies which have investigated the role of these hormones on adult neurogenesis has been performed in the DG of hippocampus (Galea, 2008, whereas only a few of them have addressed this issue in the SVZ neurogenic niche (Smith et al, 2001, Hoyk et al, 2006, Brock et al, 2010, Veyrac and Bakker, 2011, Tatar et al, 2013.…”

“…In the SVZ neurogenic niche such studies have been mostly performed in females by specifically focusing on the effect of E 2 in both naïve and neurodegenerative models (Saravia et al, 2004, Hoyk et al, 2006, Suzuki et al, 2007, Brock et al, 2010, Veyrac and Bakker, 2011. Only indirect evidences indicate that other gonadal hormones, such as progesterone and T can regulate neurogenesis in the adult SVZ niche (Peretto et al, 2001, Giachino et al, 2004, Zhang et al, 2010, Tatar et al, 2013.…”

“…Only indirect evidences indicate that other gonadal hormones, such as progesterone and T can regulate neurogenesis in the adult SVZ niche (Peretto et al, 2001, Giachino et al, 2004, Zhang et al, 2010, Tatar et al, 2013. Similarly to the DG, the modulatory effect of gonadal hormones, particularly of E 2 , on SVZ neurogenesis appears highly variable depending on type of treatment/dose (chronic vs. acute), sex, species, and (in mouse) strain considered (Smith et al, 2001, Hoyk et al, 2006, Brock et al, 2010, Veyrac and Bakker, 2011, Tatar et al, 2013. In addition, such modulation differentially impacts the neurogenic process influencing progenitor cells proliferation and/or integration of newborn neurons in both the main and the accessory OB (Hoyk et al, 2006, Brock et al, 2010, Veyrac and Bakker, 2011.…”